期刊
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
卷 51, 期 -, 页码 327-336出版社
ELSEVIER
DOI: 10.1016/j.jddst.2019.03.014
关键词
LOX-1; Small unilamellar vesicle; Surface plasmon resonance; Self-assembled monolayers
资金
- Platform for Dynamic Approaches to Living System from the Ministry of Education, Culture, Science and Technology (MEXT), Japan
- Japan Society for the Promotion of Science [18K19301]
- Grants-in-Aid for Scientific Research [18K19301] Funding Source: KAKEN
The lectin-like oxidized low-density lipoprotein (OxLDL) receptor (LOX-1) is the primary OxLDL receptor of vascular endothelial cells. OxLDL binding to LOX-1 promotes atherogenesis by upregulating LOX-1 expression to further sensitize cells against OxLDL. In this work, we demonstrate that small unilamellar vesicles (SUVs) composed of the phospholipid DOPG (1,2-dioleyl-sn-glycero-3-[phospho-rac-(1-glycerol)) (DOPG-SUV) inhibit the binding of acetylated LDL (AcLDL, a chemically stable surrogate for OxLDL) to LOX-1 on cells. DOPG-SUVs internalize into the cells expressing high levels of LOX-1 even in the presence of an excess amount of AcLDL. DOPG-SUV thus functions as a nano-carrier to deliver therapeutic agents selectively to cells in atherosclerotic lesions. The difference in the binding affinities between DOPG-SUV and AcLDL to LOX-1 clusters were quantitatively elucidated by surface plasmon resonance experiments using a sensor harboring the LOX-1 extracellular domains doped on self-assembled monolayers, which mimics the presence of LOX-1 clusters on cells. DOPG-SUV has a negatively charged surface and is larger in diameter than that of AcLDL. DOPG-SUVs interact with more receptors in the LOX-1 cluster than that envisaged for AcLDL or OxLDL binding, which explains the higher affinity of DOPG-SUV to the LOX-1 cluster when compared with those of modified LDLs.
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